Postgraduate Program in Pharmaceutical Science, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
School of Health Sciences, Pharmacy Course, Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil.
J Ethnopharmacol. 2024 Nov 15;334:118558. doi: 10.1016/j.jep.2024.118558. Epub 2024 Jul 10.
Tagetes erecta L. (Asteraceae), popularly known as Aztec Marigold, is used in folk medicine to treat several ailments including inflammatory processes. Despite its historical use, the specific mechanisms through which it may modulate inflammation, particularly its effects on neutrophils and macrophages activation, have not yet been completely investigated.
This study aimed to elucidate the anti-inflammatory mechanism of the hydroalcoholic extract obtained from T. erecta flowers, focusing on its role in the regulation of neutrophil and macrophage functions.
The production of TNF, IL-6, CXCL-1, IL-1β, IL-10 (ELISA) and NO (Griess reaction), adhesion molecule expression (CD62L, CD49d and CD18, flow cytometry), and chemotaxis were analyzed in vitro using oyster glycogen-recruited peritoneal neutrophils or macrophages (RAW 264.7) stimulated with lipopolysaccharide (LPS) and treated with the extract (1, 10 or 100 μg/mL). The resolution of inflammation was accessed by efferocytosis assay. The in vivo anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally treated with the T. erecta extract (30, 100 or 300 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (TNF, IL-6 and IL-1β, ELISA) and protein exudation (Bradford reaction) were quantified in the inflamed exudate.
In vitro studies demonstrated that the extract inhibited neutrophil chemotaxis and reduced the production and/or release of cytokines (TNF, IL-1β, CXCL1, and IL-6) as well as nitric oxide (NO) by neutrophils and macrophages when stimulated with LPS. Neutrophils treated with LPS and incubated with the extract showed an increase in CD62L expression, which leads to the impairment of neutrophil adhesion. The extract also enhanced efferocytosis of apoptotic neutrophils by macrophages, which was accompanied by increased IL-10 secretion and decreased TNF levels. In vivo studies yielded similar results, showing reduction in neutrophil migration, protein exudation, and cytokine release (TNF, IL-6, and IL-1β).
Together, the data herein obtained shows that T. erecta flower extract has anti-inflammatory effects by regulating inflammatory mediators, limiting neutrophil migration, and promoting efferocytosis. The in vivo results suggest that an herbal medicine made with T. erecta could represent an interesting pharmacological tool for the treatment of acute inflammatory condition.
万寿菊(Asteraceae),俗称 Aztec Marigold,在民间医学中用于治疗多种疾病,包括炎症过程。尽管它有历史用途,但它调节炎症的具体机制,特别是它对中性粒细胞和巨噬细胞激活的影响,尚未完全研究清楚。
本研究旨在阐明万寿菊花的水醇提取物的抗炎机制,重点研究其在调节中性粒细胞和巨噬细胞功能中的作用。
使用牡蛎糖原招募的腹腔中性粒细胞或巨噬细胞(RAW 264.7),通过脂多糖(LPS)刺激并使用提取物(1、10 或 100μg/ml)处理,在体外分析 TNF、IL-6、CXCL-1、IL-1β、IL-10(ELISA)和一氧化氮(Griess 反应)的产生、粘附分子表达(CD62L、CD49d 和 CD18,流式细胞术)和趋化性。通过吞噬作用测定评估炎症消退。通过用 Carrageenan 处理雄性瑞士小鼠的皮下组织,用 T. erecta 提取物(30、100 或 300mg/kg)口服处理,研究体内抗炎活性。在炎症渗出物中定量白细胞浸润(光学显微镜)、化学介质(TNF、IL-6 和 IL-1β,ELISA)的分泌和蛋白质渗出(Bradford 反应)。
体外研究表明,当用 LPS 刺激时,该提取物抑制中性粒细胞趋化性,并减少由 LPS 刺激的中性粒细胞和巨噬细胞产生和/或释放的细胞因子(TNF、IL-1β、CXCL1 和 IL-6)和一氧化氮(NO)。用 LPS 处理并与提取物孵育的中性粒细胞表达 CD62L 增加,导致中性粒细胞粘附受损。提取物还增强了巨噬细胞对凋亡中性粒细胞的吞噬作用,这伴随着 IL-10 分泌增加和 TNF 水平降低。体内研究也得到了类似的结果,显示中性粒细胞迁移、蛋白质渗出和细胞因子释放(TNF、IL-6 和 IL-1β)减少。
综上所述,本文获得的数据表明,万寿菊花提取物通过调节炎症介质、限制中性粒细胞迁移和促进吞噬作用来发挥抗炎作用。体内结果表明,用万寿菊制成的草药可能是治疗急性炎症的一种有趣的药理学工具。